Pared in between the two groups. Benefits: Seven-day graft survival prices within the FK group have been drastically improved compared with those of rats not receiving FK 409 (control group; 80 versus 28.six , P 0.018). Inside the FK group, IgG2C Proteins Biological Activity portal stress was considerably decreased within the first 60 minutes right after reperfusion whereas in the control group, transient portal hypertension was observed. Intragraft expression (both mRNA and protein) of early growth response-1, endothelin-1, endothelin-1 receptor A, tumor necrosis factor- , macrophage-inflammatory protein-2, and inducible nitric oxide synthase was significantly downregulated accompanied with up-regulation of heme oxygenase-1, A20, interferon- -inducible protein-10, and interleukin-10 throughout the initial 24 hours immediately after reperfusion. Hepatic ultrastructure, particularly the integrity of sinusoids was nicely protected inside the FK group.Conclusions: Low-dose FK 409 rescues small-for-size grafts in liver transplantation by attenuation of portal hypertension and amelioration of acute phase inflammatory response by down-regulation of Egr-1, together with prior induction of heat shock proteins. (Ann Surg 2004;240: 159 68)In the Departments of Surgery and Medicine, Centre for the Study of Liver Disease, University of Hong Kong Health-related Centre, Queen Mary Hospital, Hong Kong, China. Supported by the Research Grant Council and Distinguished Analysis Achievement Award of the University of Hong Kong, and Sun CY Research Foundation of Hepatobiliary and Pancreatic Surgery, the University of Hong Kong. Reprints: Prof. S.T. Fan, Department of Surgery, University of Hong Kong Healthcare Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. E-mail: [email protected]. Copyright 2004 by Lippincott Williams Wilkins ISSN: 0003-4932/04/24001-0159 DOI: 10.1097/01.sla.0000129673.13552.che mechanism of small-for-size graft injury soon after liver transplantation has been investigated recently both in animal experiments and clinical study.14 The degree of graft harm was inversely associated with graft size in liver transplantation. Transient portal hypertension in the early phase after liver transplantation and subsequent up-regulation of vasoconstriction genes and serious inflammatory response resulted in small-for-size graft failure. Therapeutic techniques focusing on attenuation of portal hypertension with each other with acute phase inflammatory response haven’t been investigated thoroughly in liver transplantation using small-for-size grafts. Early development response-1 (Egr-1) can be a zinc-finger transcription aspect. It really is a master switch coordinating up-regulation of divergent gene households associated with ischemia-reperfusion injury.five The shear tension related to hemodynamic force resulting from transient portal hypertension can induce overexpression of Egr-1.6 In our CD3g Proteins Recombinant Proteins previous animal study, early over-expression of Egr-1 was discovered in small-for-size grafts after liver transplantation.3 Nitric oxide (NO), a vaso-relaxing aspect, has been demonstrated to down-regulate shear stressinduced Egr-1 expression through inhibition of the extracellular signal-regulated kinase signaling pathway.6 Blockade of NO pathway exacerbated hepatic apoptosis and accelerated ischemia-reperfusion injury in liver transplantation.7 FK 409, a potent NO releaser, has been demonstrated to attenuate ischemia-reperfusion injury by improving microcirculation and prior induction of heat shock proteins (Hsps) which are advantageous to intracellular homeostasis.8 0 A current in vitro.